Studies of dicentric Robertsonian translocations provide evidence for a funcitonal centromeric hierarchy and structural heterogeneity
- Case Western Reserve Univ., Cleveland, OH (United States)
To characterize the pericentromeric structure of Robertsonian translocations, we used dual color fluorescence in situ hybridization (FISH) to analyze centromeric activity and delineate breakpoints in 39 dicentric translocations. In the majority of translocations (36/39), one fluorescent {alpha}-satellite signal consistently lacked typical centromeric constriction. In the Robertsonian translocations involving chromosome 14, its centromere was almost always active (24/31); in contrast, the chromosome 15 centromere was rarely the active centromere (1/12). These data strongly support a hierarchy of centromeric activity in Robertsonian translocations. Furthermore, the preferential activity of a particular centromere is both meiotically stable and consistent within multiple tissues. Breakpoints in 22 dicentric translocations were localized using probes to two satellite III DNA subfamilies, chromosome 15-specific classical satellite, and {beta}-satellite DNA. The breaks in translocations involving chromosome 14 occurred within the more distal satellite III DNA array (6/10), while three of the four remaining chromosome 14 translocations demonstrated breakpoints in proximal satellite III DNA. Most chromosome 15 breakpoints occurred in classical satellite (satellite III) DNA. These results indicate that the structure of Robertsonian translocations is heterogeneous within repetitive DNA subfamilies, although satellite III DNA is the general site of chromosomal breakage and exchange. Immunofluorescence using CREST antibodies to CENPs A, B, and C has confirmed the FISH assignments of active centromeres in four translocations studied thus far. While {alpha}-satellite DNA has been implicated as a major component of functional centromeres, our data suggest that the selection of active and inactive centromeres of dicentric chromosomes may require additional centromeric elements or specific (i.e. breakpoint-dependent) structural chromosomal features.
- OSTI ID:
- 133412
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0140
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
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